The common scientific theme which unites the research projects of this proposed Asthma and Allergic and Immunologic Diseases Cooperative Research Center is the basic and clinical investigation of human primary immunodeficiency diseases. The overall goal of these studies to identify the cellular and, ultimately, the molecular bases for the diseases under study. This information will be used to identify more definitive diagnostic features and more rational and effective therapies than those currently available. Buckley will investigate and define the immunobiology of human sever combined immunodeficiency (SCID), correlating phenotypic and functional findings from studies of blood lymphocytes with those of molecular analyses. Haynes will analyze thymic and peripheral microenvironments of deceased infants with severe primary T cell immunodeficiency, focussing particularly on those without a known molecular defect and those who did not experience T cell reconstitution after marrow stem cell transplantation, to determine whether abnormalities in such structures could be at fault. Markert will use thymic transplantation in complete DiGeorge syndrome as a model in which to study early events in human T cell development as well as to gain more definitive information about efficacy of this therapy for this lethal disease, and Williams, the Demonstration and Education Research Component, will investigate the importance of IgE mediated hypersensitivity to cockroach allergens in the disproportionately increasing prevalence of asthma among minority and inner city populations by determining the amount and nature of cockroach allergens in such households and determining the effect of reducing the quantity of such allergens on airways hypersensitivity of those affected. We believe that our proposed Center, an outgrowth of long-standing informal collaboration between the involved investigators, brings together an extremely strong and interactive group of allergists/immunologists who are physician scientists. The availability of one of the largest populations of patients with rare primary immunodeficiency disorders in this country for the studies proposed, as well as the longstanding interest of all of the investigators in allergic diseases, are additional major features that strengthen this proposal.